During the transition of chronic intestinal inflammation to colitis-associated cancer, STAT3 could be persistently activated by sphingosine-1-phosphate (S1P) produced by upregulation of sphingosine kinase 1 (SphK1), which was linked to production of the multifunctional NF-kB-regulated cytokine IL-6, and consequently upregulating of the S1P receptor, S1PR1 [31]. Here, IL6 is linked to inflammatory response.